Furosemide inhibits regenerative cortical spreading depression in anaesthetized cats.
Ionic perturbations occur during cortical spreading depression (SD), a phenomenon implicated in migraine pathophysiology. We studied the effect of 0.2, 2 and 20 mg kg-1 i.v. (n=4) furosemide on cortical direct current (d.c.) potential, cerebrovascular laser Doppler flux (rCBF[LDF]), artery diameter and NO concentration in the parietal cortex of the anaesthetized cat during repetitive SD. In vehicle-treated animals (n=4), SD activity was sustained for 50+/-1.8 min. However, duration of SD activity was significantly reduced when compared to vehicle to 39+/-6.6 (n=4), 34+/-8.5 (n=4) and 27.3+/-11.3 min (n=4), at 0.2, 2 and 20 mg kg-1 i.v. furosemide respectively. It is hypothesized that the mechanism of inhibition of SD d.c. activity by furosemide may be through alterations in cortical ion buffering capacity or inhibition of cell swelling in neurones or glia. These mechanisms may represent potential novel drug targets in future migraine therapy.
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S J
SJ
Neurosciences Research, SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK.
Smith
M I
MI
Benham
C D
CD
Hunter
A J
AJ
Parsons
A A
AA
D000704:Analysis of Variance; D000777:Anesthetics; D000818:Animals; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D013181:Cortical Spreading Depression / Q000187:drug effects*; D005665:Furosemide / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects*
D000777:Anesthetics; D005665:Furosemide